The overall objective of this proposal is to discover the important steps in the regulation of gene action in general and of the globin genes in particular. Since regulation at the level of translation of cytoplasmic mRNA appears to involve only fine tuning of protein synthesis, this application concentrates on early steps in gene action; namely, transcription of globin genes and two aspects of post-transcriptional processing, 5'-end capping and methylation and 3'-end polyadenylation of globin mRNA. Biochemical events associated with these processes should provide answers to questions concerning normal regulation of globin synthesis in erythroid cell development and in fetal development and disordered regulation which occurs in the thalassemia syndromes in man.